Gao NARASD Lithium Study
Study Details
Study Description
Brief Summary
This study is a 4-month open-label study of lithium in the acute treatment of patients with bipolar I or II disorder. Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L. Blood samples are collected at baseline and at the end of study. Analyses of 45 molecule expressions in mononuclear blood cells at baseline and endpoint will be carried out after the completion of study. Fifty patients meeting Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for bipolar I or II will be enrolled.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Lithium Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L |
Drug: Lithium
Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L
|
Outcome Measures
Primary Outcome Measures
- Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium [Baseline and Week 16]
Molecule expression is measured as a function of relative fluorescence intensity. The number derives from a photomultiplier tube which essentially counts photons. Higher numbers mean a higher intensity. The values in the results tables represents change in fluorescence intensity between Baseline and Week 16 across various molecules of interest and compares responders (those who experience a >=50% decrease in mood symptom severity between baseline and week 16) and non responders (those who did NOT experience a >=50% decrease in mood symptom severity between baseline and week 16). The rows represent the various molecules that were analyzed.
Eligibility Criteria
Criteria
Inclusion Criteria:
For inclusion in this study, subjects must meet all of the following criteria:
-
Able to provide informed consent before beginning any study-specific procedures;
-
Male or female, 18-70 years old;
-
Meets current DSM-5 criteria for bipolar I or II disorder as assessed by the The M.I.N.I. International Neuropsychiatric Interview (MINI);
-
Any symptomatic phase of bipolar I or II disorder including, depressive, manic, mixed or hypomanic
-
Global Clinical Impression-Severity for Bipolar Disorder (CGI-S-BD) ≥3;
-
Willing to take lithium;
-
If a sexually active female of childbearing potential, be using a reliable method of contraception;
-
Women with reproductive potential must have a negative urine pregnancy test;
-
Willing to have blood drawn:
Exclusion Criteria:
Any of the following is regarded as a criterion for exclusion from the study:
-
Unwilling to comply with study requirements;
-
Renal impairment (serum creatinine >1.5 mg/dL);
-
Thyroid stimulating hormone (TSH) over >20% above the upper normal limit (participants maintained on thyroid medication must be euthyroid for at least 3 months before Visit 1;
-
Other contraindication to lithium,
-
Patients who have had severe adverse reaction to Lithium;
-
Patients who require inpatient care;
-
Drug/alcohol dependence requiring immediate acute detoxification;
-
Pregnancy as determined by serum pregnancy test or breastfeeding;
-
History of nonresponse to lithium at doses ≥ 900 mg/d for ≥ 8 weeks;
-
Unwilling to have blood drawn
-
Patients with chronic medical conditions such as diabetes, coronary artery disease, immune diseases, infectious diseases and neurological disorders;
-
Active suicidal ideation with a plan or intent, a suicide attempt within past 6 months or more than 2 suicide attempts within the past 2 years.
-
Currently on lithium
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Cleveland Medical Center Department of Psychiatry | Cleveland | Ohio | United States | 44106 |
Sponsors and Collaborators
- Keming Gao
- CellPrint Biotechnology
- National Alliance for Research on Schizophrenia and Depression
Investigators
- Principal Investigator: Keming Gao, MD, PhD, University Hospitals Cleveland Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.- 07-16-05
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lithium |
|---|---|
| Arm/Group Description | Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L |
| Period Title: Overall Study | |
| STARTED | 24 |
| COMPLETED | 12 |
| NOT COMPLETED | 12 |
Baseline Characteristics
| Arm/Group Title | Lithium |
|---|---|
| Arm/Group Description | Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L |
| Overall Participants | 24 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
38.9
(12.99)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
14
58.3%
|
| Male |
10
41.7%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
7
29.2%
|
| White |
16
66.7%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
4.2%
|
| Region of Enrollment (participants) [Number] | |
| United States |
24
100%
|
| Bipolar Diagnosis (Count of Participants) | |
| Bipolar I Disorder |
17
70.8%
|
| Bipolar II Disorder |
7
29.2%
|
| Lifetime Generalized Anxiety Disorder (GAD) Diagnosis (Count of Participants) | |
| Count of Participants [Participants] |
16
66.7%
|
| Lifetime Social Phobia Diagnosis (Count of Participants) | |
| Count of Participants [Participants] |
13
54.2%
|
| Lifetime Attention Deficit Hyperactivity Disorder (ADHD) Diagnosis (Count of Participants) | |
| Count of Participants [Participants] |
14
58.3%
|
Outcome Measures
| Title | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium |
|---|---|
| Description | Molecule expression is measured as a function of relative fluorescence intensity. The number derives from a photomultiplier tube which essentially counts photons. Higher numbers mean a higher intensity. The values in the results tables represents change in fluorescence intensity between Baseline and Week 16 across various molecules of interest and compares responders (those who experience a >=50% decrease in mood symptom severity between baseline and week 16) and non responders (those who did NOT experience a >=50% decrease in mood symptom severity between baseline and week 16). The rows represent the various molecules that were analyzed. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| While we planned to analyze ~45 molecules of interest, poor quality of antibodies to some proteins & financial limitations limited us to only 28 proteins. The number of participants analyzed for protein expression differs from baseline characteristic and varies below as not all subjects had high enough levels of a particular protein to be analyzed. |
| Arm/Group Title | Lithium Non Responders | Lithium Responders |
|---|---|---|
| Arm/Group Description | Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L. | Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L. |
| Measure Participants | 9 | 12 |
| NLRP3 |
30.73
(5.66)
|
26.00
(7.25)
|
| PDEB4 |
28.15
(9.12)
|
27.31
(5.78)
|
| BAK |
11.16
(2.08)
|
11.50
(2.88)
|
| p-Fyn Yes |
12.49
(4.46)
|
13.33
(6.44)
|
| HMGB1 |
23.18
(8.69)
|
22.61
(6.58)
|
| IRS2 |
25.29
(5.64)
|
24.06
(8.71)
|
| p-CREB |
30.78
(4.34)
|
30.46
(6.55)
|
| PPAR g |
21.90
(4.31)
|
21.13
(5.62)
|
| TNFAIP3 |
33.74
(6.16)
|
31.17
(6.64)
|
| TPH1 |
7.13
(1.04)
|
7.23
(2.47)
|
| PKC theta |
33.8
(7.11)
|
35.81
(8.71)
|
| Bcl-2 |
39.72
(6.89)
|
35.87
(8.94)
|
| iNOS |
24.51
(4.38)
|
24.54
(7.54)
|
| NR3C1 |
7.33
(2.16)
|
6.69
(2.64)
|
| mTor |
22.87
(6.41)
|
21.07
(8.60)
|
| PKA C-a |
24.51
(5.69)
|
23.93
(7.08)
|
| Bcl-2 A1 |
1.37
(0.20)
|
1.19
(0.30)
|
| BDNF |
37.78
(6.72)
|
34.00
(7.44)
|
| GSK-3b |
20.89
(7.88)
|
19.49
(6.47)
|
| XBP1 |
1.11
(0.36)
|
0.96
(0.20)
|
| MARCKS |
1.32
(0.35)
|
1.28
(0.54)
|
| p-GSK 3b |
4.01
(0.78)
|
4.11
(1.54)
|
| p-GSK 3ab |
2.29
(0.64)
|
1.93
(0.55)
|
| Fyn |
33.01
(5.42)
|
30.24
(6.44)
|
| Timeless |
1.41
(0.12)
|
1.42
(0.40)
|
| PGM1 |
30.96
(4.57)
|
28.58
(6.64)
|
| NFKB p-P65 |
15.03
(6.01)
|
14.58
(8.01)
|
| Calmodulin |
34.44
(5.68)
|
31.86
(7.70)
|
Adverse Events
| Time Frame | 16 weeks | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Lithium | |
| Arm/Group Description | Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels > 0.6 mEq/L | |
All Cause Mortality |
||
| Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/24 (0%) | |
Serious Adverse Events |
||
| Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/24 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 20/24 (83.3%) | |
| Eye disorders | ||
| Blurred Vision | 1/24 (4.2%) | |
| Gastrointestinal disorders | ||
| Diarrhea | 2/24 (8.3%) | |
| Stomach Upset | 1/24 (4.2%) | |
| General disorders | ||
| Increased Thirst | 6/24 (25%) | |
| Dry Mouth | 2/24 (8.3%) | |
| Increased Daytime Sleepiness | 1/24 (4.2%) | |
| Dizziness | 1/24 (4.2%) | |
| Hair Loss | 1/24 (4.2%) | |
| Psychiatric disorders | ||
| Cognitive Impairment | 1/24 (4.2%) | |
| Renal and urinary disorders | ||
| Increased urination | 2/24 (8.3%) | |
| Reproductive system and breast disorders | ||
| Decreased Sexual Interest | 1/24 (4.2%) | |
| Skin and subcutaneous tissue disorders | ||
| Itching | 1/24 (4.2%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Keming Gao, MD, PhD |
|---|---|
| Organization | University Hospitals Cleveland Medical Center |
| Phone | 2168442865 |
| keming.gao@UHhospitals.org |
- 07-16-05